PT  - JOURNAL ARTICLE
AU  - Ming-Shih Hwang
AU  - Jérôme Boulanger
AU  - Jonathan Howe
AU  - Anna Albecka
AU  - Mathias Pasche
AU  - Leila Mureşan
AU  - Yorgo Modis
TI  - MAVS polymers smaller than 80 nm induce mitochondrial membrane remodeling and interferon signaling
AID  - 10.1101/506568
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 506568
4099  - http://biorxiv.org/content/early/2018/12/26/506568.short
4100  - http://biorxiv.org/content/early/2018/12/26/506568.full
AB  - Double-stranded RNA (dsRNA) is a potent proinflammatory signature of viral infection. Oligomerization of RIG-I-like receptors on cytosolic dsRNA nucleates self-assembly of the mitochondrial antiviral signaling protein (MAVS). In the current signaling model, the caspase recruitment domains of MAVS form helical fibrils that self-propagate like prions to promote signaling complex assembly. However, there is no conclusive evidence that MAVS forms fibrils in cells or with the transmembrane anchor present. We show here with super-resolution light microscopy that MAVS activation by dsRNA induces mitochondrial membrane remodeling. Quantitative image analysis at imaging resolutions as high as 32 nm shows that in the cellular context MAVS signaling complexes and the fibrils within them are smaller than 80 nm. The transmembrane domain of MAVS is required for its membrane remodeling, interferon signaling and proapoptotic activities. We conclude that membrane tethering of MAVS restrains its polymerization and contributes to mitochondrial remodeling and apoptosis upon dsRNA sensing.